This invention relates to hyperthermia therapy in which the temperature of living tissue is increased for therapeutic purposes, and particularly to apparatus and method for microwave hyperthermia treatment.
Hyperthermia treatments have for many years been used for treatment of cancers. It is known that raising of the temperature of cells to above about 43.degree. to 45.degree. C. for sufficient time causes necrosis, and temperatures below about 41.5 generally do not affect cells. Some types of malignant cells reportedly can be destroyed by raising their temperatures to levels slightly below those injurious to most normal cells. One of the techniques which has been used for hyperthermia is heating of the blood of a patient by an external apparatus, thereby raising the temperature of the entire body or a portion thereof to the therapeutic temperature. This procedure risks substantial injury to the patient if temperature is not carefully controlled, and may fail to raise the temperature of the malignant cells sufficiently for destruction. Any malignant cells which remain undestroyed may cause a recurrence of the tumor, growth or malignancy (hereinafter tumor).
Some surface tumors may be successfully treated by application of surface heat from a heated object. Deeply located tumors, however, are difficult to heat to therapeutic temperatures without destruction of the overlying tissue.
Another hyperthermia technique uses electromagnetic radiation to heat tissue. The electromagnetic radiation is often in the form of radio frequency (RF) or microwave radiation because of the ease of generating, controlling and directing microwaves, and also because of the absorption characteristics of tissue at microwave frequencies. At the current state of the art, microwave hyperthermia is usually at frequencies in the range of 100 MHz to 5 GHz. Microwave hyperthermia when applied to tissue containing a tumor generates heat within the tissue which raises the temperature of the tissue generally. It has been found that tumors tend to have a limited blood supply by comparison with healthy tissue. Thus, the circulation of blood through a tumor is low by comparison with circulation through healthy tissue. At any microwave power density, the tumor will usually be hotter than the surrounding healthy tissue because the more ample flow of blood in the healthy tissue provides cooling of the healthy tissue. Thus the tumor may be heated by microwave hyperthermia to a therapeutic temperature without significant effect on surrounding healthy tissue.
It has been found that microwave hyperthermia when used in conjunction with either radiotherapy or with chemotherapy provides more consistent success than either alone. A course of treatment may include several radiotherapy treatments each week, interspersed with microwave hyperthermia treatments. Widespread practical application of such combined therapy depends upon the availability of convenient and predictable microwave hyperthermia methods and apparatus.
U.S. Pat. No. 4,448,198 issued May 15, 1984, to Turner describes an invasive hypertherapy arrangement in which a plurality of microwave applicators are inserted into body tissue. The surgical implantantion requires the use of an expensive operating room and the services of a skilled surgeon, which is not convenient. The applicators provide numerous potential sites for infection and at least require care by the patient. The implanted applicators may interfere with concurrent radiotherapy. Since the dielectric constant of the tumor may differ from that of the surrounding tissue, the energy from the microwave applicators may be partially reflected by the tumor if the applicators are implanted in healthy adjacent tissue, and this may result in an undesirable temperature distribution.
Noninvasive microwave hyperthermia relies upon heating from applicators placed outside the patient's body. This is particularly convenient for small surface tumors, the extent of which can be readily seen. The applicator is often held in contact with the surface being treated to avoid excessive spreading of the energy. For small tumors, a single applicator may be used. The center of the applicator is directed towards the tumor, and the power is applied. Adjacent normal tissue is likely to be at a lower temperature than the temperature at the tumor because a simple applicator such as a horn has a power distribution which decreases away from the center or axis. The temperature of the tumor may be monitored by a small sensor inserted into the tumor. However, if the temperature sensor is electrically conductive it may itself be heated, thereby providing an erroneous indication that the tumor is being heated Also, the electrically conductive temperature sensor may perturb the field, for example by signal reflection, and therefore cause constructive interference at a location away from the axis of the application. This may undesirably damage normal tissue. If the probe is thermally conductive it may undesirably cool the tumor.
Large tumors are more difficult to treat. When an applicator such as a horn with a single aperture is used, the power distribution across the aperture of the applicator may heat the center of the area to too high a temperature, and thereby cause burning, or may not heat outlying portions of the tumor to therapeutic temperatures. Failure to sufficiently heat portions of the tumor allows regrowth of the tumor. Burned areas subject to radiation therapy tend to heal slowly or not at al. Ordinarily, radiation therapy is discontinued if the area to be irradiated is injured. Any burning of a part of the tumor by microwave hyperthermia is therefore undesirable, as it may limit therapeutic options. Other variables include surface phenomena such as reduction of surface temperature by perspiration, reflection of microwave energy by bone structures, and the use of heating or cooling pads applied to the surface being treated. A major cause of temperature differences is variation of blood flow to various portions of the tissues being heated. Thus, the treatment of large tumors presents difficulties not found in small tumors.
One known technique for hyperthermia treatment of large tumors is to use a "blanket" applicator which is large enough to cover the entire area to be treated. Such large area applicators are ordinarily made up of an array of a number of relatively small antennas. While such an applicator is theoretically plausible, there are practical difficulties. Since the antennas are spaced one from another on the blanket, those portions of the surface to be treated which lie immediately under an antenna element receive substantially more power than those areas lying between antenna elements and therefore tend to be heated more than outlying areas. Attempts to improve the power distribution by phasing the antennas (as in the Turner patent) to provide constructive reinforcement of the hyperthermia energy at points between antenna elements often fail. The failure comes about because the effective path length of the hyperthermia power passing through a dielectric medium depends upon the dielectric constant of the medium. When the medium is tissue, the dielectric constant varies from point to point and also depends upon the type of tissue (fat, muscle, etc.) through which the field passes. This results in a relatively random distribution of heating, and in the occurrence of hot spots at which burning of the tissue may occur, and also in cold spots at which therapeutic temperatures are not obtained. Such burns may not be visible and may undesirably remain unhealed for long periods if concurrent radiotherapy takes place.
An applicator for providing a uniform microwave field over a relatively large area is described in U.S. Pat. No. 4,271,848 issued June 9, 1981, to Turner. Ideally, such a field should provide uniform heating of a region of tissue. The heating effect will not be uniform, however, because of differences in the amount of absorption of power from the field by various different types of tissue. Even assuming that the heating attributable to the applicator is uniform over the surface to be treated, therapeutic results are not likely to be optimum, because of differences in the vascularization (number and size of bood vessels) and blood flow of various portions of the tissue or surface being heated. A plentiful supply of blood vessels and plentiful supply of blood to one portion of the tissue may result in much lower equilibrium temperatures during hyperthermia than an adjacent area with a paucity of blood vessels and poor supply of blood. Thus, the combination of uneven heating of the tissue by the applicator and of variable amount of cooling by the blood supply results in widely varying temperatures across the surface or throughout the tissues being treated.
A method for treating large tumors is described in U.S. Pat. No. 4,397,314 issued Aug. 9, 1983, to Vaguine. This technique implants temperature sensors in the tumor and in the surrounding tissue. A microwave generator under control of the temperature sensors is coupled to a plurality of external applicators and controls the energy applied to each applicator to provide therapeutic temperatures inside the tumor with an overriding protection of the surrounding healthy tissue. Individual microwave applicators are evaluated during the hyperthermia treatment to determine their effect on the overall heating pattern for optimizing the heating pattern. Besides being invasive, this arrangement has the disadvantage that implanted temperature sensors may have to be moved during the course of the treatment as the tumor size is reduced and healthy tissue replaces it. Since the size of the tumor and the physiological condition of the patient change during the course of the therapy, the optimization of the applicators must be done anew during each session of therapy. This is labor-intensive, and the optimization is subject to human error.